Expired PAR-09-135: Replication, Fine-Mapping and Sequencing: Follow-Up on Genome-Wide Association Studies for Arthritis and Musculoskeletal and Skin Diseases (R01)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (http://www.niams.nih.gov)

Title: Replication, Fine-Mapping and Sequencing: Follow-Up on Genome-Wide Association Studies for Arthritis and Musculoskeletal and Skin Diseases (R01)

Announcement Type
New

Update: The following updates relating to this announcement have been issued:

July 10, 2012 - This PAR has been reissued as PAR-12-236.
September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011. Adobe B1 forms are required for due dates on or after May 8, 2011.
August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.
June 22, 2010 - See Notice NOT-AR-10-039 The purpose of this notice is to extend the second receipt date.
June 18, 2010 - See Notice NOT-AR-10-040 The purpose of this notice is to announce an increase in the budget limit for applications submitted in response to this PAR.
December 7, 2009 - This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions.

Program Announcement (PA) Number: PAR-09-135

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.846

Key Dates
Release/Posted Date: March 20, 2009
Opening Date: August 29, 2009 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): August 31, 2009; June 1, 2010; June 1, 2011
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): September 29, 2009; June 29, 2010 (Changed to July 27, 2010 per NOT-AR-10-039); June 29, 2011
Peer Review Date(s): February/March 2010, October/November 2010, October/November 2011
Council Review Date(s): May 2010, January 2011, January 2012
Earliest Anticipated Start Date(s): July 2010, April 2011, April 2012
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: June 30, 2011

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. This Funding Opportunity Announcement (FOA), issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, encourages applications that propose to perform replication, fine-mapping, and sequencing studies of human genomic regions that are putatively associated with phenotypes relevant to the NIAMS mission. Genomic regions of interest are primarily those identified by genome-wide association studies (GWAS). The objective of this FOA is to enhance the identification of causal genes and genetic variants that influence complex diseases relevant to the NIAMS mission. Replication, fine-mapping, and sequencing studies are to be conducted in existing cohorts with defined phenotypes. This FOA will not support recruitment of human subjects, collection of medical or phenotypic data, studies using animal models, or the initial discovery phase of GWAS.
Mechanism of Support. This FOA will utilize the NIH Research Project (R01) grant mechanism. In some instances, an active NIAMS R01 award may currently support a GWAS with a two-stage design, including initial discovery and replication. In such instances, investigators may submit a revision (formerly competing supplement) application in response to this FOA, to support additional replication, fine-mapping, or sequencing efforts, provided the application conforms to both the budgetary requirements of this FOA and the format requirements of revision applications.
Funds Available and Anticipated Number of Awards. For this funding opportunity, the NIAMS expects to commit approximately $1.5 million total costs in each of fiscal years 2010, 2011, and 2012, to support three to four new projects per year. Budgets up to $250,000 direct costs per year and project periods of up to two years may be requested. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
Budget and Project Period. Applications may request direct costs up to $250,000 per year and project duration of up to two years.
Application Research Strategy Length: The R01 application Research Plan component of the PHS398 (Item 3) may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts. Seehttp://grants1.nih.gov/grants/funding/funding_program.htm
Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.
Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).
Renewals. Renewal (formerly competing continuation) applications will not be accepted for this FOA.
Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
Application Materials. See Section IV.1 for application materials.
All applications, including resubmission, revision and renewal, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions.
General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:
- SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
- General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

This Funding Opportunity Announcement (FOA) will support replication, fine-mapping, and sequencing studies of human genomic regions that are putatively associated with common complex traits, primarily those identified by genome-wide association studies (GWAS). The purpose is to accelerate the discovery of causal genes and genetic variants that influence diseases and disorders within the NIAMS mission, and improve our understanding of the molecular mechanisms of disease. These studies are expected to be undertaken in existing cohorts in which phenotypic data have already been collected; thus, this FOA will not support recruitment, clinical characterization of subjects, studies using animal models, or discovery GWAS efforts. Awards under this FOA will provide support for personnel, genotyping, sequencing, analyses and other costs, as justified by the study design.

Background

A GWAS is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits, or the presence or absence of a disease or condition. The genome-wide association approach has proven to be powerful in systematically identifying common genetic variants of modest effect that influence the risk of many complex diseases. There are many areas of the NIAMS mission (http://www.niams.nih.gov/About_Us/Mission_and_Purpose/long_range.asp) in which GWAS could furnish novel insights; and some significant advances have already been made in rheumatoid arthritis, systemic lupus erythematosus (SLE), psoriasis and osteoporosis, as a result of GWAS.

While the potential of GWAS to identify risk loci in complex diseases is becoming evident, it is clear that many challenges lie ahead. The NIAMS has considered the resources required for success, and has put in place an FOA that supports genome-wide association analyses that make use of existing genotype/phenotype datasets (http://grants.nih.gov/grants/guide/pa-files/PAR-08-123.html).

Recently, a roundtable discussion convened extramural investigators from across NIAMS mission areas to assess GWAS challenges and opportunities. Participants pointed out that while GWAS in a number of areas have yielded promising results, follow-up studies are needed to translate initial findings of GWAS into the biological insights that could lead to predictive, diagnostic, and therapeutic advances. For instance, in the initial analysis of a GWAS, many of the observed associations may be false positives. Thus, it is necessary to conduct replication studies to discern the true positives, typically by testing a subset of the most strongly associated single nucleotide polymorphisms (SNPs) or other genetic variants in one or more additional populations of samples. In addition, in the regions of confirmed associations, the causal variants will only occasionally be among those that are directly genotyped. Moreover, GWAS detect almost exclusively the effects of common SNPs, but offer limited power to capture any rare variants (<1% population frequency) and structural variants, such as insertions, deletions, copy number variants, microsatellites, segmental duplications, transposons, and inversions. Detailed sequencing may be necessary to characterize the genetic variations in the disease-associated regions, and enhance the identification of disease causal variants.

Objectives

This FOA will provide support for replication, fine-mapping, and sequencing studies of the genomic regions found through GWAS that have the potential to identify genes and genetic variants that influence the risk for rheumatic, musculoskeletal, and skin diseases. For this FOA, the term replication is defined as testing a subset of the most strongly associated SNPs or other genetic variants in one or more additional study populations. The term fine-mapping is defined as additional genotyping of SNPs or other genetic variants, which have not been included in the original genotyping platform, near a gene or a region that has been replicated for association with a disease or trait. Diseases of interest include, but are not limited to: rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondyloarthritis, gout, scleroderma, psoriasis, vitiligo, alopecia areata, osteoporosis, and osteoarthritis. An application may propose, for example, a replication study alone, or a replication study plus fine-mapping and sequencing efforts, or fine-mapping plus sequencing studies. These follow-up studies are needed to validate the initial associations revealed from GWAS, narrow the association intervals of interest, identify genes and genetic variants associated with disease, and extend the findings to diverse populations (different races, ethnicities, or environmental exposures) and related phenotypes. Well-designed replication studies should follow the published guidelines (NCI-NHGRI Working Group on Replication in Association Studies, Nature 447, 655-660, 2007) for what constitutes replication of a genotype-phenotype association and how it can be best achieved.

Applicants are expected to have access to DNA collections, phenotypic and genotypic data, or exposure data from existing cohorts of sufficient size at the time of submission, in order to adequately address the specific aims. Applicants who plan to seek data from the NIH GWAS data repository will be expected to follow the published guidance (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-013.html). Specifically, applicants should anticipate the need to submit a data access request and a Data Use Certification that is co-signed by the investigator and the designated Institutional Official. In the Approach section of the Research Strategy, the applicants should briefly address plans for requesting access to data and state their intention to abide by the Data Use Certification. Applicants who intend to access data in the NIH GWAS data repository for the research proposed are advised to secure that access prior to submitting their application for NIH support.

Applications are expected to reflect the inclusion of appropriate expertise such as collaborative groups of clinicians, geneticists, statisticians, and bioinformaticians, in order to ensure that the complexities of phenotypic definition, the study design, and statistical genetic analysis are adequately considered. Each application should clearly define the rationale for the proposed replication, fine-mapping, and sequencing studies, provide detailed information or a sufficient summary of the GWAS that identified the genomic regions associated with a particular disease or trait, and explain why those regions should be assigned priority for a replication study, or fine-mapping and sequencing effort. For a replication study, the application should also clearly describe the study population chosen for replication, in comparison with the initial discovery cohort, any known replication effort(s), either published, in progress, or planned, and the statistical power of the replication sample set to detect a smaller genetic effect than reported in the original study, in order to address potential publication bias. For sequencing and fine-mapping studies, applications should also describe the rationale for the proposed study design, including the extent and scope of resequencing efforts, efficient fine-mapping strategies, the choice of statistical methods for data analysis, and the costs associated with sequencing and genotyping. The investigators are encouraged to seek resources for high quality and cost effective sequencing and genotyping.

Applications responding to this FOA may seek support for, but not limited to:

Specimen preparation and transfer;
Sequencing effort for identification of SNP and other genetic variants;
Genotyping of selected genetic polymorphisms;
Data analyses; and
Appropriate support for the Principal Investigator and other key personnel (this part of requested budget is expected to be modest).

This FOA is not appropriate for :

The initial discovery phase of GWAS efforts;
Efforts to recruit human subjects and collect medical or phenotypic data;
Studies involving animal models.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This FOA will use the NIH Research Project Grant (R01) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

In some instances, an active NIAMS R01 award may currently support a GWAS with a two-stage design, including initial discovery and replication. In such instances, investigators may submit a revision (formerly competing supplement) application in response to this FOA, to support additional replication, fine-mapping, or sequencing efforts, provided the application conforms to both the budgetary requirements of this FOA and the format requirements of revision applications.

This FOA uses Just-in-Time information concepts (see SF424 (R&R) Application Guide). It also uses the modular, as well as the non-modular, budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) should use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

The NIAMS intends to commit approximately $1.5 million total costs in each of fiscal years 2010, 2011 and 2012, to fund three to four projects per year. Applications may request direct costs up to $250,000 per year and project duration of up to two years.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

NIH grants policies described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Public/State Controlled Institutions of Higher Education
Private Institutions of Higher Education
Hispanic-serving Institutions
Historically Black Colleges and Universities (HBCUs)
Tribally Controlled Colleges and Universities (TCCUs)
Alaska Native and Native Hawaiian Serving Institutions
Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Small Businesses
For-Profit Organizations (Other than Small Businesses)
State Governments
Indian/Native American Tribal Governments (Federally Recognized)
Indian/Native American Tribally Designated Organizations
County Governments
City or Township Governments
Special District Governments
Independent School Districts
Public Housing Authorities/Indian Housing Authorities
U.S. Territory or Possession
Indian/Native American Tribal Governments (Other than Federally Recognized)
Regional Organizations
Non-domestic (non-U.S.) Entities (Foreign Organizations)

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model.Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically.Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.

Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and competing renewal applications will be permitted addressing the previous peer review critique (Summary Statement) in only a single amendment (A1). See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-003.html and NOT-OD-09-016. Original new and competing renewal applications that were submitted prior to January 25, 2009 will be permitted two amendments (A1 and A2). For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date.

In some instances, an active NIAMS R01 award may currently support a GWAS with a two-stage design, including initial discovery and replication. In such instances, investigators may submit a revision (formerly competing supplement) application in response to this FOA, to support additional replication, fine-mapping or sequencing effort, provided the application conforms to both the budgetary requirements of this FOA and the format requirements of revision applications.

Renewals. Renewal (formerly competing continuation) applications will not be accepted for this FOA.

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

Grants.gov (http://www.grants.gov/applicants/get_registered.jsp) and
eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered

Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
Direct questions regarding Grants.gov registration to:
Grants.gov Customer Support
Contact Center Phone: 800-518-4726
Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
Direct questions regarding the Commons registration to:
eRA Commons Help Desk
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
Email [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

The individual(s) designated as PDs/PIs on the application must be registered also in the NIH eRA Commons.In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.
Each PD/PI must hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account.
When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization.PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons.
This registration/affiliation must be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PD(s)/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY: (301) 451-5936

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application components, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PIs assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., Special Instructions, regarding appropriate required budget component.)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic [non-U.S.] Entities)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

Request budgets in U.S. dollars;
Prepare detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms not the PHS398 Modular Budget component)(see NOT-OD-06-096);
Not include any charge-back of customs and import fees;
Comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF;
If appropriate, request funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) ( see NOT-OD-01-028, March 29, 2001);
Comply with Federal/NIH policies on human subjects, animals, and biohazards; and
Comply with Federal/NIH biosafety and biosecurity regulations (see Section VI.2., Administrative and National Policy Requirements)

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in Item 13 of the SF424 (R&R) Cover component.All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI.Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission.The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component.Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan, must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts.The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component.All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form.See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only.Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 3.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review and Anticipated Start Dates
Opening Date: August 29, 2009 (Earliest date an application may be submitted to Grants.gov)
Letter of Intent Receipt Date(s): August 31, 2009; June 1, 2010; June 1, 2011
Application Due Date(s): September 29, 2009; June 29, 2010; June 29, 2011
Peer Review Date(s): February/March 2010, October/November 2010, October/November 2011
Council Review Date(s): May 2010, January 2011, January 2012
Earliest Anticipated Start Date(s): July 2010, April 2011, April 2012

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research.
Name, address, and telephone number of the PD(s)/PI(s).
Names of other key personnel.
Participating institutions.
Number and title of this funding opportunity.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Justine Buschman, M.S.
Division of Skin and Rheumatic Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza, Suite 800
6701 Democracy Blvd.
Bethesda, MD 20892-4872
Telephone: (301) 496-4811
Fax: 301-480-1284
Email: [email protected]

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp and follow Steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

3.C.1 Submitting On-Time

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time(of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed. All applications must meet the following criteria to be considered on-time:

All registrations must be complete prior to the submission deadline

The application must receive a Grants.gov tracking number and timestamp (or eRA help desk ticket confirming a system issue preventing submission) by 5:00 p.m. local time on the submission deadline date.

Any system identified errors/warnings must be corrected and the submission process completed within the error correction window.

Please visit http://era.nih.gov/electronicReceipt/app_help.htm for detailed information on what to do if Grants.gov or eRA system issues threaten your ability to submit on time.

Submission to Grants.gov is not the last step - applicants must follow their application through to the eRA Commons to check for errors and warnings and view their assembled application!

3.C.2 Two Day Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

Once an application package has been successfully submitted through Grants.gov NIH provides applicants a two day error correction window to correct any eRA identified errors or warnings before a final assembled application is created in the eRA Commons. The standard error correction window is two (2) business days, beginning the day after the submission deadline and excluding weekends and standard federal holidays. All errors must be corrected to successfully complete the submission process. Warnings will not prevent the application from completing the submission process.

Note that the following caveats apply:

Initial application submission must be on-time.

The AOR/institutions is expected to enforce that application changes made within the error correction window are restricted to those necessary to address system-identified errors/warnings. NIH may reject any application that includes additional changes.

Proof of on-time submission (e.g., Grants.gov timestamp and tracking number) and description of all changes made within the window must be documented in the PHS 398 Cover Letter component of the application.

3.C.3 Viewing an Application in the eRA Commons

Once any eRA identified errors have been addressed and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further processing.

If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days, excluding Federal holidays.

Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two-day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed or if information was lost or compromised during transmission. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors), it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.

If the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or did not transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.

If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.

Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements and Information.

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

PHS398 Research Plan Component Sections

Application Research Strategy Length: The R01 application Research Plan component of the PHS398 (Item 3) may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations. An application that does not comply with the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

Foreign Applications (Non-domestic [non-U.S.] Entities)

Indicate how the proposed project has specific relevance to the mission and objectives of the NIH/IC and has the potential for significantly advancing the health sciences in the United States.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by CSR and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below

As part of the scientific peer review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, will be discussed and assigned an impact/priority score;
Receive a written critique; and
Receive a second level of review by the appropriate national advisory council or board.

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as determined by scientific peer review.
Availability of funds.
Relevance of the proposed project to program priorities.

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance. Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Specific to this FOA: What advantages does the project offer for replication, fine-mapping and sequencing studies of genetic regions putatively associated with the complex trait(s) under investigation? What advantages does the study offer for discriminating true positive results from the large number of false positive results expected with GWAS? What advantages does it offer for follow-up studies to identify causative genetic variants and develop diagnostic, preventive, or therapeutic strategies?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) Protections for Human Subjects, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Specific to this FOA: Are the study design and population chosen well described and appropriate for the aims proposed? Have any potential biases in subject selection been identified, and is the approach for minimizing these biases appropriate? Are environmental factors and other covariates that might influence the phenotype also available for analysis? Are the phenotype and exposure measures of sufficient quality and completeness to provide maximum scientific value from the addition of targeted genotyping?

Environment. Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Revision Applications. When reviewing a Revision application (formerly called a competing supplement application), the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations
As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agents Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Applications from Foreign Organizations. Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

William J. Sharrock, Ph.D.
Division of Musculoskeletal Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza, Suite 800
6701 Democracy Blvd.
Bethesda, MD 20892-4872
Telephone: (301) 594-5055
Fax: (301) 480-4543
Email: [email protected]

Yan Wang, M.D., Ph.D.
Division of Skin and Rheumatic Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza, Suite 800
6701 Democracy Blvd.
Bethesda, MD 20892-4872
Telephone: (301) 594-5032
Fax: 301-480-1284
Email: [email protected]

2. Peer Review Contact(s):

Richard Panniers, Ph.D.
Center for Scientific Review, NIH
6701 Rockledge Drive MSC7890
Bethesda, MD 20892-7720
Telephone: (301) 435-1741
Fax: (301) 480 2067
Email: [email protected]

3. Financial/Grants Management Contact(s):

Andrew Jones
Acting Chief Grants Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza, Suite 800
6701 Democracy Blvd.
Bethesda, MD 20892-4872
Telephone: (301) 594-3535
Fax: (301) 480-5450
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Vertebrate Animals:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the impact/priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women, Minorities, and Children:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicines PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles.Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.